(a) Field of the Invention
This invention relates to 4(or 5)-(pyridinyl)-2-pyrimidinamines and their cardiotonic use.
(b) Information Disclosure Statement
4-(4-Pyridinyl)-2-pyrimidinamine (no. 4a) and N-methyl-4-(4-pyridinyl)-2-pyrimidinamine (no. 4g) were reported by Bennett et al. [J. Med. Chem. 21, 623-628 (1978)] to be active when tested for antiinflammatory activity against carrageenan-induced edema in the rat but were said to be inactive when tested against adjuvant-induced edema in the rat. Other compounds reported active against carrageenan-induced edema were 4-(3-pyridinyl)-2-pyrimidinamine (4e), 5-methyl-4-(4-pyridinyl)-2-pyrimidinamine (4p), as well as the N-acetyl and N-propionyl derivatives (4h and 4i) of 4-(4-pyridinyl)-2-pyrimidinamine. Discussion of the antiinflammatory activity of the compounds disclosed in this publication concluded as follows:
"None of the compounds tested against adjuvant-induced edema in the rat displayed a level of activity sufficient to warrant further investigation. Based on additional testing it would appear that these compounds represent a series of false positives in the carageenan-induced edema model."
Compounds 4a and 4g of Bennett et al. were prepared by reacting 3-dimethylamino-1-(4-pyridinyl)-2-propen-1-one with guanidine or 1-methylguanidine, respectively. Compound 4e was prepared by reacting 3-dimethylamino-1-(3-pyridinyl)-2-propen-1-one with guanidine and compound 4p was prepared by reacting 3-dimethylamino-2-methyl-1-(4-pyridinyl)-2-propen-1-one with guanidine.
Isomeric 2-(4- or 3-pyridinyl)-4-pyrimidinamines are shown as anti-allergic agents in the Lesher and Singh U.S. Pat. No. 4,086,233, issued Apr. 25, 1978, and U.S. Pat. No. Re. 30,024, reissued June 5, 1979, of U.S. Pat. No. Re. 4,032,523, issued June 28, 1977.
N-Acetyl-2-(4-pyridinyl)-4-pyrimidinamine and other N-alkanoyl compounds are shown as intermediates in the Lesher and Singh U.S. Pat. No. 4,118,571, issued Oct. 3, 1978.